In clinicopathological analyses, PPG are associated with clearly lower incidences of early dumping syndrome (EDS), gastritis in the remnant stomach and reflux esophagitis (RE) as well as a significant decrease in postoperative malnutrition due to loss of appetite and postoperative body weight loss [1] [2] [3] [4] . Patients after PPG have been reported to have a better postoperative quality of life (QOL) [1] [2] [3] [4] . However, there is a demerit in patients after PPG. The most common demerit in patients after PPG is postprandial abdominal fullness (PAF: early satiety, postprandial fullness and diet limitation are frequent symptoms) due to gastric stasis in the remnant stomach (GSRS) [1] [2] [3] [5] [6] [7] . Frequencies of PAF after PPG have been reported at 30% to 60% [1] [2] [3] [5] [6] [7] [8] . PAF has been reported to be closely associated with food intake [9] . Food consumption per meal then becomes insufficient and leads to a marked deterioration of the postoperative QOL, which is one of the major problems in patients after PPG. Therefore, it is considered that PAF may be caused by GSRS due to delay of the gastric emptying function (GEF).

Generally well-known GEF tests are the radioisotope method where gastric emptying of a semisolid diet or solid diet is examined, and the acetaminophen method where gastric emptying of a liquid diet is examined [10] [11] . The radioisotope and acetaminophen methods are physiological and quantitative tests that are noninvasive and cause no bitterness to patients [9] . For the GEF test with a solid diet (rice gruel is substituted in Japanese), a radioisotope method using ^99mTc tin colloid has been used. In order to examine GEF with a liquid diet, the acetaminophen method has been used with orange juice. It is reported that PPG patients show a GEF delay in a solid and semisolid diet [1] [2] [3] [5] [6] [7] [8] . The main cause of postgastrectomy disorders (PGD), especially PAF, due to delayed GEF after PPG has been considered to be the length of the antral cuff (LAC) [2] [11] [12] [13] . However, the optimal LAC still unknown [13] .

Aim of the study

We studied the correlations between LAC and PGD including PAF and GSRS, and between LAC and GEF of the residual stomach in patients who underwent PPG for early gastric cancer.

From January 2001 to December 2015, 50 patients with early gastric cancer without lymph node metastasis in the lower and/or middle stomach visited our hospital. Fifty patients (30 men and 20 women aged 33 to 79 years with a mean age of 66.7 years) with early gastric M (mucosa) or SM1 (submucosa 1; macroscopically, 1/2 or less submucosal invasion of cancer) cancer of N0 (no lymph node metastasis) underwent PPG with preservation of the pyloric, hepatic and celiac branches of the vagal nerve (PHCV) (M cancer, D1 lymph node dissection; SM1 cancer, D1 + α lymph node dissection in radical curability) [3] . They were divided into 2 groups based on the LAC [Group A (n = 24), LAC was 1.5 to 2.5 cm [average average 2.0 ± 0.3 cm (short LAC)]; Group B (n = 26), LAC was 2.6 to 3.5 cm [average 3.0 ± 0.4 cm (long LAC)] and the correlations between LAC and PGD and between LAC and GEF were compared. Their postoperative courses showed no complications except for one case (wound infection) in group A and 2 cases (wound infection) in group B. No adjuvant therapies including anticancer chemotherapy were applied in either group. The past histories included no diseases of the psychoneurological, metabolic (diabetes mellitus, hypothyroidism) or gastrointestinal systems such as gastrointestinal functional disorders (non-ulcer dyspepsia, irritable bowel syndrome, chronic constipation, and functional intestinal disease) or malignant tumor.

Follow up periods were from 1.5 to 5 years after PPG. This study was performed to each patient at 1.5 years after PPG.

Even for early gastric cancer located in the middle and/or lower stomach, the distal part of the stomach including the pylorus has conventionally been resected with D2 lymph node dissection without preserving PHCV (i.e., conventional distal gastrectomy) [1] . PGD such as malnutrition due to loss of appetite, weight loss, EDS, RE, or GRS are unfavorable sequelae in patients after conventional distal gastrectomy [1] [2] . To prevent PGD in early gastric cancer, therefore, PPG is now performed wordwide including in Japan. However, some inadequacy of preventing PGD, especially PAF, has been reported in patients one year or more after PPG [1] [2] [3] [4] [6] [7] [11] [12] . The causes of PGD such as PAF in patients after PPG have been studied, focusing on the vagal nerve, infrapyloric vesscels (artery and vein), and LAC [2] [6] [11] [12] [15] [16] [17] [18] [19] .

It is considered that PGD, especially PAF with GSRS, after PPG is due to damage to PHCV and infrapyloric vesscels (artery and vein) as a result of skeletonization of the subpyloric region with the subpyloric lymph node dissection [15] [16] . It is also reported that PHCV are necessary for pyloric sphincter functioning in patients after PPG [11] [12] . In recent years the vagal nerves, including hepatic and pyloric branches, have been preserved to prevent PGD including PAF and endoscopic GSRS [13] . Nakabayashi et al. [6] suggested that gastric stasis during the early postoperative period in patients after PPG without preservation of the pyloric branch of the vagal nerve is due to tonic and phasic contractions of the pylorus. In contrast, it was concluded that preservation of the vagal nerve such as PHCV is not necessary for gastro-pyloroduodenal motility in patients after PPG [2] [3] [4] [5] [6] . Morita et al. [17] also showed that PAF due to GSRS can be present up to 5 years after PPG even with preservation of the PHCV. Therefore, the roles of PHCV in PPG are not clearly understood. Moreover, it is well-known that the vagal nerves such as PHCV are an important factor in intestinal peristalsis [20] . In addition, it is reported that preservations of the infrapyloric artery and vein are important to prevent the postoperative gastric stasis after PPG [15] [16] . Ischemia around pylorus may lead to pyloric dysfunction. In this study, all subjects were early gastric cancer (M and SM1) without lymph node metastasis. Therefore, we preserved PHCV and both the infrapyloric artery and vein in all PPG patients.

Preserving the pyloric sphincter prevents EDS due to the rapid emptying of food and prevents RE, alkaline GRS due to reflux of duodenal juice into the remnant stomach and esophagus [1] . It was reported that the remnant stomach emptying function was favorable when a 2.0-cm or longer pyloric antrum was preserved, and favorable QOL results were obtained in patients after PPG [2] [11] [12] . Nakane et al. [12] pointed out that in PPG with transection 1.5 cm proximal to the pyloric ring, PAF and a high incidence of food residue in the remnant stomach after meals were common compared with PPG with transection 2.5 cm proximal to the pyloric ring, resulting in poor food intake and body weight recovery. They further demonstrated that PPG with transection 2.5 cm proximal to the pyloric ring was superior to that with transection at 1.5 cm in terms of postprandial symptoms, food intake, body weight recovery and gastric emptying. They concluded that the length of the retained antrum (i.e., LAC) plays an important role in the motility of the pyloric ring following PPG. According to this data, the size of LAC may be related to the delayed gastric emptying of a diet. Although the LAC gradually increased, from 1.5 cm during the initial use of the procedure to 3.0 cm or more currently, its optimal length still remain unclear [13] [17] . As for the interviews in this study, PAF was observed at a rate of 100% in patients with a short LAC (1.5 to 2.5 cm) and at 7.7% in those with a long LAC (2.6 to 3.5 cm). According to this data, the author divided patients after PPG into 2 groups (short LAC and long LAC) in the present studies. To clarify the causes of PGD, especially PAF, studies in PPG patients with preservation of the vagal nerve have been performed focusing on LAC. PAF, appetite and food consumption per meal were clearly better with a long LAC than a short LAC. Symptomatic RE, EDS, and decreased percent body weight versus pre-illness were found more often with a short LAC than with a long LAC.

Antropyloroduodenal coordination is very important to transport gastric contents to the duodenum [21] . GEF, especially PAF, may be a motility disorder such as antropyloroduodenal coordination in patients after PPG. In this study, on findings of esophagogastric endoscopy, endoscopic RE and GRS were more frequenty detected in PPG with a short LAC than with a long LAC. GSRS was clearly more frequent in PPG with a short LAC than in that with a long LAC. In accordance with the interviews of PGD and esophagogastric endoscopic findings, PPG patients with a short LAC may experience discoordination of antropyloroduodenal motility compared with those with a long LAC. We suggests that a long LAC may be necessary to coordinate antropyloroduodenal motility for preventing PGD such as PAF.

The postoperative pathophysiology of the GEF of a solid diet in patients after PPG has been assessed in detail. Generally, ^99mTc tin colloid or ^99mTc-DTPA is used for the solid diet as a nuclide [10] . As the acetaminophen method can be safely performed at a reasonable cost, it is widely used for the determination of the emptying time of a liquid diet instead of the radioisotope method [9] . As a solid diet, we used rice gruel because it is familiar to Japanese people, easy to eat after gastric surgery, and easy to cook and prepare for the experiment. In a previous study, the gastric emptying curve with a rice gruel diet presented a regression line with a high regression coefficient in the control subjects, and author thus considered that there was no problem associated with the use of a rice gruel diet, being the same as a solid diet [22] . The time to 50% residual rates revealed GEF with a solid diet [9] [10] . In the present study, the author used the time to 50% residual rates to evaluate GEF in patients after PPG. To examine the liquid diet-emptying function with the acetaminophen method, diets such as milk, liquid food, elemental diet, and orange juice are used. Acetaminophen is not entirely absorbed by the stomach but is promptly absorbed by the small intestine [9] . It is suggested that the blood concentration of acetaminophen at 45 minutes shows the GEF with a liquid meal [9] . We used the same method in this study. Mistiaen et al. [23] also showed that liquid diets are more appropriate for detecting possible rapid gastric emptying rates and EDS. A solid diet test, on the other hand, can be used to study gastric stasis. To clarify the reasons for the persistent PAF and GSRS in the present study, the author investigated the GEF after PPG. The gastric emptying of the solid diet was significantly delayed in PPG with a short LAC compared with a long LAC. However, the gastric emptying of the liquid diet showed no difference between PPG with a short LAC and PPG with a long LAC. Thus, in PPG patients, preservation of a long LAC is considered to be useful to prevent delay of the gastric emptying. It is possible that a feeling of PAF after PPG with a short LAC due to the long-term retention of solid food may occur due to delayed emptying of the solid diet. Therefore, slow emptying of a solid diet in patients after PPG, especially those with a short LAC, may contribute to the sensation of PAF due to GSRS. Regarding GEF with a liquid diet [blood concentration of acetoaminophen at 45 minutes (μg/ml)], there were also no significant differences among patients after PPG with a short LAC, those with a long LAC, and normal subjects. In this study, GEF with the solid food was clearly delayed in patients with a short LAC compared with that in patients with a long LAC. However, there was no difference in liquid empting time between PPG patients with a short LAC and those with a long LAC.

This was a retrospective study. A randomized control trial comparing the postoperative states after PPG with a short LAC and with a long LAC should be performed in the future. Moreover, the mechanism of antropyloroduodenal coordination and/or motility in humans is complicated and its control probably involves the functioning of the neural systems including central, peripheral, and entric nervous systems [7] [21] [24] . Studies from various aspects are thus required to clarify the correlations between these factors and PGD such as PAF with GSRS after PPG in the future.

PAF, appetite and food consumption per meal were clearly more favorable in PPG patients with a long LAC [3.0 ± 0.3 cm (2.6 to 3.5 cm)] than a short LAC [2.0 ± 0.4 cm (1.5 to 2.5 cm)]. Symptomatic RE, EDS, decreased percent body weight compared with pre-illness, endoscopic RE and GRS were more frequent in PPG patients with a short LAC than in those with a long LAC. GSRS was clearly more prevalent in PPG patients with a short LAC than in those with a long LAC. GEF with solid food was clearly delayed in PPG patients with a short LAC compared with a long LAC. However, there was no difference in the liquid empting time between PPG patients with a short LAC and those with a long LAC. Patients with a short LAC showed a poor postoperative QOL and delayed gastric emptying of a solid food compared to those with a long LAC.

The authors have read the manuscript and have approved this submission. And there are no no conflicts of interest in association with this study.

Ryouichi Tomita have operated these cases and analyzed all data. Shigeru Fujisaki and Kenichi Sakurai did assistant of the operation.

Tomita, R., Sakurai, K. and Fujisaki, S. (2017) Relationships between Length of the Antral Cuff and Postgastrectomy Disorders and Gastric Empting Function in Patients after Pylorus-Preserving Gastrectomy for Early Gastric Cancer. Journal of Cancer Therapy, 8, 867-879. https://doi.org/10.4236/jct.2017.810076